KIEL, Germany -- Bilateral pallidal neurostimulation to reduce movement symptoms outdid sham stimulation in patients with primary generalized or segmental dystonia, researchers reported.
KIEL, Germany, Nov. 8 -- Bilateral pallidal neurostimulation to reduce movement symptoms outdid sham stimulation in patients with primary generalized or segmental dystonia, according to researchers here.
Compared with baseline, three months of treatment reduced the severity of dystonia symptoms as seen by a 39% improvement in movement scores, a 38% reduction in disability, and a 30% improvement in physical quality of life, reported Jens Volkmann, M.D., of Christian Abrechts University, and colleagues, in the Nov. 9 issue of the New England Journal of Medicine.
Recruited from 2002 to 2004, 40 patients with primary segmental or generalized dystonia received an implanted device for deep-brain stimulation and were randomly assigned to receive either neurostimulation or sham stimulation for three months, the researchers wrote. The disorder is characterized by twisting repetitive movements caused by involuntary muscle contractions.
Sixteen patients had segmental dystonia, which affects the neck in combination with the face, shoulder, arm, or upper trunk, the researchers said. Patients with segmental dystonia, compared with those with generalized dystonia, were older at the onset of the disease (mean 32.6 versus 12.3 years, P<0.001). They also had a shorter duration of disease (16.3 years versus 21.9 years, P=0.05).
The patients had previously taken multiple medications, which had been discontinued because of inefficacy or adverse effects. Thirty-five patients had received injections of botulinum toxin, but 21 had stopped using the drug because symptom control was insufficient.
Movement was rated on the Burke-Fahn-Marsden Dystonia Rating Scale (range, 0 to 120, with higher scores indicating greater impairment). Two investigators who were unaware of treatment status assessed the severity of dystonia by reviewing videotaped sessions.
Neurostimulation was delivered via permanent quadripolar electrodes implanted bilaterally in the posteroventrolateral portion of the internal globus pallidus during one session, while the patient was under general anesthesia. The electrodes were then connected to a fully implanted neurostimulator during the same or a subsequent surgical session.
Three months after randomization, the change from baseline in the mean (SD) movement score was significantly greater in the neurostimulation group (?15.8 14.1 points) than in the sham-stimulation patients (?1.4 3.8 points, P<0.001), the researchers reported.
Likewise, disability scores improved significantly in the neurostimulation group, by a mean of 3.92.9 points (a 37.5% reduction in disability), compared with a mean of 0.81.2 points (8.3%) in the sham-stimulation group (P<0.001).
Neurostimulation was significantly superior on all symptom subscores of the Burke-Fahn-Marsden Dystonia Rating Scale (P<0.001) and most of the disability items. Quality of life, as assessed on the basis of the score for the physical component of the SF-36, improved in the neurostimulation group by 10.17.4 points (a 29.8% improvement), which differed significantly from the change in the placebo group (3.88.4 points, an 11.4% improvement).
When patients who were originally assigned to sham treatment were switched to active neurostimulation after three months (the open-label extension phase), there were similar benefits after six months of treatment. At the six-month mark, the original neurostimulation group sustained the benefits marked in the first three months, the researchers reported.
The combined analysis of the entire cohort after six months of neurostimulation showed substantial improvement in all movement symptoms (except speech and swallowing), and in the level of disability and quality of life.
After six months, the mean improvement in the movement score was 46% compared with baseline. Half of the patients had more than a 50% reduction in symptoms, a benefit that translated into significant improvement in all activities of daily living, Dr.Volkmann said.
During the three-month randomization phase, nine adverse events were reported in eight patients, of which three events occurred in the sham stimulation group. Three patients had infection at the stimulator, requiring removal of the implant in two patients. All adverse events resolved without permanent damage, the researchers reported.
During the extension phase, 11 patients had 13 adverse events. The most frequent adverse event, dysarthria (slurred, but understandable speech) occurred in five patients. Overall, the adverse events during this phase of the study were typically related to stimulation and resolved or improved by changing stimulation measures.
Although the six-month follow-up may have been too short to assess the full range of improvement in all aspects of dystonia, these results, Dr.Volkmann said, match the only other study of pallidal deep-brain stimulation, which was for primary generalized dystonia. That study reported an average 51% reduction in the movement score after 12 months.
The investigators reported that they found no changes in cognitive status associated with the deep-brain procedure. In contrast to a recent report suggesting an increased risk of suicide after pallidal neurostimulation, the investigators found that mood improved significantly among the patients in their study, with no behavioral abnormalities.
In conclusion, they said, bilateral high-frequency stimulation of the internal globus pallidus is an effective therapy. Extended follow-up studies are now needed to assess the long-term efficacy and safety of this treatment, they concluded.
This study was supported by an unrestricted research grant to Dr. Volkmann and co-author Reiner Benecke, M.D., from Medtronic and by other university grants. Various other study authors reported having received speaking fees and consulting fees from Medtronic, which markets the electrodes and the neurostimulator used in the study.